Partitioning of Catechol Derivatives in Lipid Membranes: Implications for Substrate Specificity to Catechol- O-methyltransferase

Petteri Parkkila*, Tapani Viitala

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

8 Citations (Scopus)

Abstract

We have utilized multiparametric surface plasmon resonance and impendance-based quartz crystal microbalance instruments to study the distribution coefficients of catechol derivatives in cell model membranes. Our findings verify that the octanol-water partitioning coefficient is a poor descriptor of the total lipid affinity for small molecules which show limited lipophilicity in the octanol-water system. Notably, 3-methoxytyramine, the methylated derivative of the neurotransmitter dopamine, showed substantial affinity to the lipids despite its nonlipophilic nature predicted by octanol-water partitioning. The average ratio of distribution coefficients between 3-methoxytyramine and dopamine was 8.0. We also found that the interactions between the catechols and the membranes modeling the cell membrane outer leaflet are very weak, suggesting a mechanism other than the membrane-mediated mechanism of action for the neurotransmitters at the postsynaptic site. The average distribution coefficient for these membranes was one-third of the average value for pure phosphatidylcholine membranes, calculated using all compounds. In the context of our previous work, we further theorize that membrane-bound enzymes can utilize membrane headgroup partitioning to find their substrates. This could explain the differences in enzyme affinity between soluble and membrane-bound isoforms of catechol-O-methyltransferase, an essential enzyme in catechol metabolism.

Original languageEnglish
Pages (from-to)969-978
Number of pages10
JournalACS Chemical Neuroscience
Volume11
Issue number6
DOIs
Publication statusPublished - 18 Mar 2020
Externally publishedYes
MoE publication typeA1 Journal article-refereed

Keywords

  • Catechols
  • distribution coefficient
  • multiparametric surface plasmon resonance
  • partition coefficient
  • quartz crystal microbalance
  • supported lipid bilayer

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